title: Luminal hydrochloric acid stimulates rapid transepithelial ion fluxes in rodent esophageal stratified squamous epithelium.
abstract: It remains unclear whether enhanced ion fluxes occur in the esophageal stratified squamous epithelium upon acid exposure. Rat esophageal tissues devoid of submucosal glands displayed basal short-circuit current (Isc) of 5.03 +/- 1.93 microA/cm(2) and lumen-negative potential difference (PD) in association with net absorption of Na+ and Cl-, and secretion of HCO3(-). Luminal hydrochloric acid (HCl) challenge (pH = 1.6) triggered an acute rise of the Isc and increment of negative PD to seven-fold of baseline, which was diminished in HCO3(-)-free, but not Na+- free buffer. The rise of Isc was inhibited by pretreatment with di-isothiocyanatostilbene-2, 2'-disulphonic acid (DIDS) and 5-(N-ethyl-N-isopropyl)-amiloride (EIPA). Topical carbachol, capsaicin, forskolin or CFTR(inh)-172 had no effect on basal Isc.CFTR(inh)-172 did not reduce the acid-increased Isc. Functional ablation of capsaicin-sensitive nerves had no effect on the acid-induced Isc. The phenomenon of enhanced ion fluxes upon acid stimulation was confirmed in human esophageal specimens. Our results demonstrated that the mechanism of acid-induced rapid transepithelial ion fluxes is dependent on the presence of bicarbonate ions as well as functional anion transporters and Na+/H+ exchanger, but independent of cystic fibrosis transmembrane conductance regulator (CFTR). The capsaicin-sensitive and muscarinic-dependent nerve pathways did not play roles in the mechanism.
authors.affiliation: Graduate Institute of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: B R
authors.initials: BR
authors.lastname: Lin
authors.forename: H T
authors.initials: HT
authors.lastname: Hsieh
authors.forename: J M
authors.initials: JM
authors.lastname: Lee
authors.forename: I R
authors.initials: IR
authors.lastname: Lai
authors.forename: C F
authors.initials: CF
authors.lastname: Chen
authors.forename: L C H
authors.initials: LC
authors.lastname: Yu
mesh_terms: D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid / Q000494:pharmacology; D000293:Adolescent; D000368:Aged; D000584:Amiloride / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D017776:Autonomic Pathways / Q000187:drug effects / Q000502:physiology; D001639:Bicarbonates / Q000737:chemistry; D002021:Buffers; D002211:Capsaicin / Q000494:pharmacology; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000494:pharmacology; D015194:Diffusion Chambers, Culture; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism*; D004947:Esophagus / Q000187:drug effects / Q000378:metabolism*; D006801:Humans; D006851:Hydrochloric Acid / Q000494:pharmacology*; D006863:Hydrogen-Ion Concentration; D066298:In Vitro Techniques; D007477:Ions / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D009475:Neurons, Afferent / Q000187:drug effects; D010275:Parasympathetic Nervous System / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors
chemical_list: D001639:Bicarbonates; D002021:Buffers; D007477:Ions; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D000584:Amiloride; D017878:4,4'-Diisothiocyanostilbene-2,2'-Disulfonic Acid; D006851:Hydrochloric Acid; D002211:Capsaicin; C039614:ethylisopropylamiloride